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Journal of Lipid Research, Vol. 47, 724-733, April 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Lipids isolated from bone induce the migration of human breast cancer cells

Jeane Silva^*, Somsankar Dasgupta^*, Guanghu Wang^*, Kannan Krishnamurthy^*, Edmond Ritter and Erhard Bieberich^1,*

^* Institute of Molecular Medicine and Genetics, School of Medicine, Medical College of Georgia, Augusta, GA 30912
Department of Surgery, School of Medicine, Medical College of Georgia, Augusta, GA 30912

Published, JLR Papers in Press, January 26, 2006.

¹ To whom correspondence should be addressed. e-mail: ebieberich{at}mail.mcg.edu

Bone is the most common site to which breast cancer cells metastasize. We found that osteoblast-like MG63 cells and human bone tissue contain the bile acid salt sodium deoxycholate (DC). MG63 cells take up and accumulate DC from the medium, suggesting that the bone-derived DC originates from serum. DC released from MG63 cells or bone tissue promotes cell survival and induces the migration of metastatic human breast cancer MDA-MB-231 cells. The bile acid receptor farnesoid X receptor (FXR) antagonist Z-guggulsterone prevents the migration of these cells and induces apoptosis. DC increases the gene expression of FXR and induces its translocation to the nucleus of MDA-MB-231 cells. Nuclear translocation of FXR is concurrent with the increase of urokinase-type plasminogen activator (uPA) and the formation of F-actin, two factors critical for the migration of breast cancer cells. Our results suggest a novel mechanism by which DC-induced increase of uPA and binding to the uPA receptor of the same breast cancer cell self-propel its migration and metastasis to the bone.

Supplementary key words bile acids • deoxycholate • farnesoid X receptor • urokinase-type plasminogen activator

Abbreviations: CDC, chenodeoxycholate; DC, deoxycholate; FXR, farnesoid X receptor; HPTLC, high-performance thin-layer chromatography; MG63-CM, MG63-conditioned medium; uPA, urokinase-type plasminogen activator; uPAR, urokinase-type plasminogen activator receptor

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